The role of the glypican and syndecan families of heparan sulfate proteoglycans in cardiovascular function and disease

Abstract

Heparan sulfate proteoglycans (HSPGs) are proteoglycans formed by a core protein to which one or multiple heparan sulfate chains are covalently bound. They are ubiquitously expressed in cellular surfaces and can be found in the extracellular matrix and secretory vesicles. The cellular effects of HSPGs comprehend multiple functionalities that include 1) the interaction with other membrane surface proteins to act as a substrate for cellular migration, 2) acting as a binding site for circulating molecules, 3) to have a receptor role for proteases, 4) to act as a coreceptor that can provide finetuning of growth factor receptor activity threshold, and 5) to activate intracellular signaling pathways (Sarrazin S, Lamanna WC, Esko JD. Cold Spring Harb Perspect Biol 3: a004952, 2011). Among the different families of HSPGs, the syndecan and glypican families of HSPGs have gained increased attention in relation to their effects on cardiovascular cells and potential role in disease progression. In this review, we will summarize the effects of syndecan and glypican homologs on the different cardiovascular cell types and discuss their contribution to common processes found in cardiovascular diseases (inflammation, hypertrophy, and vascular remodeling) as well as their potential role in the development and progression of specific diseases including hypertension, heart failure, and atherosclerosis.